Interferons will be prepared in selected cell cultures belonging to host species protectable by human interferons, i.e., bovine, sheep, rabbit, swine, feline, hamster, mouse, and rat. For optimal production of interferon in these cells, Sendai, Newcastle disease and Bluetongue viruses, live or irradiated by ultraviolet light, as well as poly rI:rC, will be explored as inducing agents. The nonhuman interferons will be subjected to moderate purification prior to their use as immunogens in mice or rats. They will be examined for the degree of reverse protection in cultures of human cells including those trisomic for chromosome 21 that are especially sensitive to human interferon. In crossneutralization tests between human and nonhuman interferons and their respective antisera, we shall seek to determine the extent of their antigenic interrelationships. Human interferon antigenic and structural subspecies will be segregated and highly purified by means of antibody, hydrophobic and hydroxylapatite chromatographies. They will be compared with respect to antiviral effects in heterologous cells, and the spectrum of neutralizing antibodies provoked in mice against these effects expressed in human and nonhuman cells will be evaluated.